Interstitial hydraulic conductivity in a fibrosarcoma

Convective transport of therapeutic agents in solid tumors can be improved through intratumoral infusion. To optimize the convection, we investigated the dependence of the hydraulic conductivity on tissue deformation induced by interstitial fluid pressure gradient during the infusion. Two experimental systems were used in the investigation: 1) one-dimensional perfusion through tumor slices and 2) intratumoral infusion using a needle. With these systems, we found that the apparent hydraulic conductivity (K(app)) could be altered by several orders of magnitude in fibrosarcomas through changes in perfusion conditions. When the perfusion pressure was less than a threshold level, fluid flow in tissues could not be detected. When the perfusion pressure was increased above the threshold level, K(app) depended on perfusion system and pressure. The maximum variation in K(app) in fibrosarcomas reached 80,260-fold in our experiments. The large variation in K(app) could be explained by perfusion pressure-induced tissue deformation. These experimental data suggest that the hydraulic conductivity is very sensitive to tissue deformation and imply that it is possible to improve intratumoral infusion of therapeutic agents through optimization of infusion conditions.